It is known that the 2',3'-dideoxy analogs of the common nucleosides are effective in protecting T.sub.4.sup.+ lymphocytes against the cytopathic effects of various viruses, including HIV (human immunodeficiency virus). In the quest to find cures for viral diseases, particularly AIDS, it is desirable to simplify and economize high yield synthetic procedures for the 2',3'-dideoxynucleosides such as 2',3'-dideoxycytidine (ddC).
The art is replete with various synthetic methods for 2',3'-dideoxynucleosides, most of which are costly, low yield procedures requiring extensive manipulations. For example, 2',3'-dideoxycytidine (ddC) was first prepared in 1967 and is currently undergoing clinical trials because it appears to be the most potent anti-AIDS therapeutic to date. Six published syntheses of ddC are available, three of which use 2'-deoxycytidine as the starting material. (See Horowitz, et al., J. Org. Chem, 32, 817 (1967); Samukov, et al., Bioorq. Khim., 9, 132 (1983) or Chemical Abstracts, 98, 161094X, (1983); Prisbe et al., Syn. Commun., 15, 401 (1985); and Marumoto et al., Chem. Pharm. Bull., 22, 123 (1974)); Kawana et al., Chem. Letts., 2419 (1987); Farina et al., Tetrahedron Letters, 29, 1239 (1988).
In the synthesis of ddC the current procedures exhibit numerous disadvantages such as requiring expensive and not easily accessible starting materials, extensive manipulation including chromatography, as well as resulting in a low overall yield.
For example, one synthetic scheme for ddC involves a bromoacetylation procedure where N-protected cytidine is reacted with acetyl bromide to yield bromoacetylated intermediate compounds which are further reduced and hydrogenated to ddC. This particular procedure results in a low overall yield due largely to the poor yield of the intermediate compounds after the bromoacetylation step.
Other hydrogenation and reduction steps also used in the current procedures do not result in optimal yields of intermediate and hence final products.
Therefore, there is a need for a simple, economic, high yield synthetic procedure for the manufacture of 2',3'-dideoxycytidine.